LEE SILVER: There is no such thing as nature versus nurture; it's nature and nurture. Almost every aspect of who we are is based on an interaction between the two.

JOHN HOCKENBERRY: To sort out the nature of genes from the influence of environment, scientists have constructed twin studies, mouse studies, they even use personality tests. But will knowing what we’re made of tell us anything about who we are? Listen as we explore "DNA and Behavior."

But First.....

Consider the cruelty of the disease schizophrenia, tearing young men and women from their families, plunging them into a nightmare of paranoid delusions and sinister inner voices. Crueler still, for much of this century, science blamed parents for their children’s inner agony. We know now that schizophrenics have a brain disease, but the search of causes has lead scientists into a labyrinth of environmental factors and genetic inheritance as John Rieger reports.

[Sound of father reading Green Eggs & Ham:]

“Ok. Where were we? Would you eat them in a box?”

JOHN RIEGER: No matter how much we love and cherish them, one child in 100 will be schizophrenic. It strikes typically at the first flowering of adulthood with hallucinations and paranoid delusions that ravage family bonds. And until about twenty years ago, psychiatrists blamed it on bad mothers.

DR. E. FULLER TORREY: Were I to guess, I will guess that when she died, she still felt guilty that somehow she had caused it, because after all, that’s what the big doctor said.

JOHN RIEGER: Dr. E. Fuller Torrey saw his own sister develop schizophrenia at seventeen, and he watched his mother shoulder the blame. An avowed enemy of pumpkin headed psychiatry, he’s helped spark a revolution in how we understand schizophrenia.

DR. E. FULLER TORREY: This is a brain disease.

JOHN RIEGER: Torrey was co investigator in a landmark study of schizophrenia in twins. In sixty eight pairs of identical twins, twenty eight pairs were discordant for schizophrenia. Meaning one twin had it and the other didn’t.

DR. E. FULLER TORREY: What we found was that there were clear differences in both brain structure and function despite the fact that they have the same genes.

JOHN RIEGER: Now, that’s a puzzle because schizophrenia runs in families. In the general population it strikes one in a hundred. But children of schizophrenics are ten times more likely to be affected. So, it appears to be genetic. But the twin study shows it’s not that simple. Steven Hyman is director of the National Institute of Mental Health.

STEVEN HYMAN: Even twins who share 100% of their DNA are both affected with schizophrenia only about 40% of the time. So, that means since they share all of their DNA that some non genetic factors must be involved in producing the illness.

JOHN RIEGER: This could be good news. Maybe your genes make you vulnerable to schizophrenia, but some factor in the environment makes you sick. Find the environmental factor, and perhaps you could prevent the disease. But the missing factor may be random. Steven Hyman.

STEVEN HYMAN: You know identical twins have different fingerprints, and they have different patterns of folds in their brain. There simply isn’t enough information it the genome to encode the precise detail of…of the connections among the hundred billion neurons in the brain. And so while genes create the overall blueprint for each person, uh there is a certain amount of simply uh random developmental effects in wiring up the brain. And then, the environments acts to shape and sculpt those connections.

JOHN RIEGER: The genetics of schizophrenia is also complex. Identical twins have all the same genes. Fraternal twins share only half their genes. If a gene causes schizophrenia, then identical twins should both be schizophrenic about twice as often as fraternal twins. But in fact, the ratio is five to one, which means that schizophrenia involves not one gene but an unknown number of genes.

STEVEN HYMAN: This has been a major area of research for the last ten years, and unfortunately has not been very productive.

JOHN RIEGER: Dr. Torrey says the gene hunters won’t succeed. He believes the environmental factor in schizophrenia is a virus.

STEVEN HYMAN: I think that we can look for a gene or genes that cause schizophrenia from now for the next 150 years and we’re not going to find them. What we need to do is identify the environmental agent, viral or otherwise that actually gets in the brain. I think that over the next five years we will identify genes that cause vulnerability to schizophrenia….

JOHN RIEGER: Steven Hyman.

STEVEN HYMAN: …and this will launch an enormous flowering of research which is going to take those genes and use them as tools of inquiry in the brain to say, you know, what is it that’s going wrong in these brains? And then another group of scientists are going to be able to ask, are there modifiable environmental factors that are taking this genetic risk and making people sick uh so we’ll have a great uh flowering I hope of research on environmental factors and indeed prevention research.

[Sound of father reading Green Eggs and Ham]

JOHN RIEGER: But for now we haven’t found any genes. We don’t know what the environmental factors are. We can’t predict who will become schizophrenic, but we know it will be one in a hundred worldwide. And we know it’s not caused by bad parents.

[Sound of child laughing]

JOHN RIEGER: I’m John Rieger for the DNA Files.

[music]

JOHN HOCKENBERRY: This is the DNA Files. I’m John Hockenberry.

[Sound of airplane]

Everybody is different. I, for one, would not care to throw myself out of the open door of an airplane, flying almost three miles above the ground. Hey, but Jeff Talbot gets a thrill from doing just that. He is what some people call a “novelty seeker.”

JOHN HOCKENBERRY: Novelty-seeking, which is kind of a clinical term from people from people who like to perform stunts like jumping out of planes, is just one of the many personality traits behavioral geneticists are studying. These scientists are trying to discover if there is a connection between the way one acts and one’s genetic make-up. Long before scientists posed the question, it’s been the stuff of family lore.

[Sound of classical music under the Dinner Party Scene; Random voices overheard at a big family dinner party:

WOMAN: "But she does have your fine ear for music."

CHILD: (Laughter)

MAN: "And her Uncle Herbert's sense of humor."

JOHN HOCKENBERRY: One’s sense of humor is not something that is “passed down” from Uncle Herbert. The only thing that is actually passed down – or inherited – are genes. Scientists are just beginning to unravel the physical process of how genes influence specific traits – like a sense of humor. Human beings each have between 80,000 and 100,000 genes within each cell of our bodies. These genes are organized into 23 pairs of chromosomes, including the X and Y, the famous chromosomes that determine a person’s sex. Since the 1950s, scientists have understood that our DNA is a “code” that regulates what our body looks like and how it operates. New research in genetics, molecular biology and neuroscience shows us that genes are also a factor in the make-up of our personality. But what do we mean by “personality”? Robert McCrae, a research psychologist at the National Institute on Aging, has been studying personality for the last 20 years.

ROBERT MCCRAE: Personality traits are characteristics that differentiate one person from another and that give people continuity over time; they're enduring aspects of what you're like. So, personality traits are likely to be expressed in what you think, and in your beliefs, and attitudes, and your feelings, and your emotional vulnerabilities and reactions, all those kinds of things would potentially be part of your personality.

JOHN HOCKENBERRY: But what creates our personality? Where does it come from? After years of debate, scientists now agree that every facet of our personality is created through a complex interaction of both genetics and environment. It’s clear that we are not born “a blank slate” to be molded purely by our environment. It is also clear that our personalities are not rigidly “hard-wired” by our bodies. Our genes do not “predetermine” our fate. But they can create a “predisposition” towards a trait that gets triggered by something in the environment. For instance, a child may have a genetic propensity towards shyness. And faced with a domineering teacher, the child may become even more withdrawn. And here’s where scientists don’t agree. What has more influence on our personality, genetics or environment?” Behavioral geneticists are investigating personality traits to discover whether and to what extent our genetic make-up influences the way we act.

ROBERT MCCRAE: I could give you a list of about 18,000 trait names in the English language. You can be nervous, extroverted, silent, curious, straightforward, down to earth...... um, those kinds of characteristics.

JOHN HOCKENBERRY: This program – “DNA and Behavior: Is Our Fate In Our
Genes?” -- will take a close look at three personality traits – sexual orientation, addiction and novelty-seeking you heard about earlier. In the next hour, we'll explore the interplay of genetics and environment on these traits. We'll learn the distinction that scientists make between personality traits and culturally-based behaviors. And we'll talk to the scientists who are busy figuring out what makes us tick.

[Sounds of a parade. Shouts, drums, music.]

Voices Chanting: “People with AIDS, under attack. What do we do? Go fight back!”

Man in Crowd: ”It's OK to be Gay. There's no fear to be queer. You know, it's beautiful.”

JOHN HOCKENBERRY: More than 200,000 people from all walks of life and sexual orientations turned out to watch or march in San Francisco's 28th annual gay pride parade. But out of all those people, what makes someone gay? Male and female physical attributes are genetically determined. That much is obvious. But understanding what makes one attracted to the opposite sex or the same sex is not so straight forward. The debate over whether being homosexual is inborn or learned has
Been going on for quite some time. But are we even asking the right question? Dr. Lee Silver, Professor of Genetics at Princeton University, doesn't think so:

LEE SILVER: There is no such thing as nature versus nurture; it's nature and nurture. Almost every aspect of who we are is based on an interaction between the two. And so it's this very, very powerful interaction between genes and the environment which is always at play in almost all aspects of who we are.

JOHN HOCKENBERRY: Dr. Pilar Ossorio studies ethical issues associated with genetic medicine and genetic research at the American Medical Association's institute for ethics:

PILAR OSSORIO: It's not as though you could melt down the person and then you would have, "Oh, this bit is environmental, and this bit is genetic."

LEE SILVER: When we're talking about environment, we're talking about every single stimulus that comes into our bodies from the moment we're conceived up until we are born. We're talking about the way people talk to us, the food that we eat, the air that we breathe, the position of the
fetus inside the womb. The environment is many, many times more complicated than our genetics, and we're never going to understand it completely. So the environment is really everything other than the genes.

JOHN HOCKENBERRY: To make things more complicated, the part of the equation that is genetic is rarely influenced by a single gene. Pilar Ossorio:

PILAR OSSORIO: For the most part, it's not going to be the results of any single gene directly and only affecting some kind of characteristic. It's going to be a complex interplay between any number of genes, some of which might not seem all that related. You know, things that have to do
with sexuality might have to do with how you see colors, how you smell things, even though people might think it would be strange to say that "Oh, a gene that affects how you smell is a sexual orientation gene."

JOHN HOCKENBERRY: Popular culture sometimes confuses the "nature/nurture debate". For instance, film plots often foster the idea that personality is directly inherited from one's genes. "The Bad Seed" made back in 1956 was one such gem. Patty McCormick plays Rhoda, a darling
little girl, brought up in a perfect home with loving parents, but with an unfortunate propensity towards murder........

[Sound of suspense music]

JOHN HOCKENBERRY: Which, it turns out she inherited from an "evil" grandmother.

THE VISITOR: They cite a type of criminal born with no capacity for remorse of guilt. No feeling of right or wrong.

THE MOTHER: You really mean to say that nice family surroundings and advantages could make no difference at all?

THE VISITOR: It's just that they are bad seeds. Plain bad from the beginning. And nothing can change them.

JOHN HOCKENBERRY: Over the first half of this century, the idea that our personality is influenced by heredity moved in and out of favor in the popular culture. But modern scientific inquiry into the matter didn't begin until the 1960's. While scientists understood the basic concept of inheritance, there was no way to isolate and observe individual genes. They devised a method of examining the influence of inheritance on personality based on the study of identical twins. Until the 1950's twin studies were the only method scientists had to try to trace a biological role in behavior. Over a dozen twin studies on male sexual orientation have been done in the past 40 years.

Reporter Jackie Northam looks at one recent twin study of gay men:

JACKIE NORTHAM: Identical twins share the same genes. So by studying twins, researchers hope to determine if genes have an impact on personalities or behavioral traits.

DOUG WIDENER: One of the things that makes us different that is on the top of my head is that is that I can roll my tongue and he can't.

DAVE WIDENER: So watch Doug just do - now see that's not a very good tongue roll. That’s barely one at all, and then, look. See.

DOUG WIDENER: But I can do some things better than he can too. So…
(laughs)

JACKIE NORTHAM: Dave Widener might be able to roll his tongue better than his brother Doug. But they figure that's one of the few differences between them. The 28-year-old identical twins not only look alike but they say they enjoy the same music, food and sports. And they're both gay.
Could there be a link between their identical genes and their sexual orientation? To find out the answers to questions like this, psychologists Michael Bailey, with Northwestern University near Chicago and Richard Pillard, with Boston University, have done two twin studies on male homosexuality. Dr. Michael Bailey says they drew from a limited sample.

MICHAEL BAILEY: We recruited our twins by advertising in gay and lesbian publications and the advertisements basically said “Are you a twin - if so, call us.” In our first study we had about 50 sets of identical twins and about 50 sets of fraternal twins. We also had a third group who were not twins but these were adoptive siblings.

JACKIE NORTHAM: What Bailey and Pillard found was that the identical twin of a gay man stood about a 50% chance of being homosexual himself. Those figures dropped to about 20% for fraternal twins - they share only half their genes. Those chances dropped even further for the biological or adoptive siblings.

MICHAEL BAILEY: I would say that our results greatly increase the probability that there is a gene or that there are genes for sexual orientation in both males and females. However, it would be good to do an even better study.

JACKIE NORTHAM: Many scientists agree that more sophisticated studies need to be done before conclusive results can be made about the relationship of genes to personality traits. It's not like eye or hair color which are genetically determined. And Professor Jon Beckwith, a geneticist at Harvard Medical School, says twin studies in particular are riddled with problems.

JONOTHAN BECKWITH: To begin with, I would say that people doing the twin studies have started off with very simplistic ideas of how you go about studying very complex behaviors such as homosexuality, or intelligence, etc. I think identical twin studies where you look at twins born with exactly the same set of genes, would appear on the surface to be good kinds of experiments to do. But in fact, it turns out that there are a lot of complexities that are ignored and in fact I think they are much better at showing up in environmental effects then they are in really establishing genetic effects.

JONOTHAN BECKWITH: Environment obviously goes back to how they develop within the womb. And there are lots of studies coming out now that suggest that in the womb itself there are differences in the way different twins develop.

JACKIE NORTHAM: Bailey agrees that the environment is a crucial factor for personality traits - but he defends the studies saying they were able to determine a pattern of similarity in relatives for homosexuality.

MICHAEL BAILEY: At the conclusion of a twin study, usually what you're going to be able to say is something like ‘genes sure seem to be important or genes don't seem to be very important' - you're not going to be able to say 'there seems to be a gene on chromosome 21 that affects this trait'.

JACKIE NORTHAM: But Bailey does acknowledge problems with his studies, including how the participants were recruited. Placing ads in gay magazines created a certain bias he says. When he did a later study in Australia, using a broader spectrum of twins by searching that country's
twin registry, Bailey's findings were strikingly different than the American studies. The identical twin of a gay man in the Australian study stood about a 25% chance of being gay himself. That's about half the figure found in the American study. However, Bailey says this study also
found that just under 10% of fraternal twins had a gay brother. So, what does that mean? Even though the numbers were lower, the ratio between the identical and fraternal twins stayed constant -- still showing the genetic influence.

MICHAEL BAILEY: I think that the sampling method in this Australian study is clearly preferable to the way that we did it in America and so these new numbers, I think, are more trustworthy.

JACKIE NORTHAM: But what these numbers call into question is how misleading statistics and findings can be. Twin studies rely on something called a heritability estimate which illustrates how much a particular behavioral trait can vary - both genetically and environmentally. Scott
Stoltenberg, a behavioral geneticist at the University of Michigan, says heritability estimates were first designed by plant and animal breeders as a way of determining which traits would be good for selection - like the numbers of ears of corn or percentage of milk production. But Stoltenberg
says this system is flawed when it refers to humans.

SCOTT STOLTENBERG: The statistics then were sort of taken over by people that did human behavioral genetics because well, there really wasn't much else out there I think to try to learn about human behavior genetics with because, you know, you can't do selective breeding with humans and, you know, there are a lot of things you can't do with humans.

JACKIE NORTHAM: Even behavioral geneticists emphasize that these statistics really only apply to populations, not individuals. They cannot tell us to what extent genes influence a trait in any individual. Dr. Richard Lewontin, a molecular geneticist at Harvard University, says whatever studies are used, he has no doubt sexual orientation is a mixture of genetics and environment. But, he adds, so what?

RICHARD LEWONTIN: The question is once the studies are done, and even if they
were perfect, what would they tell you that you want to know: What is it
I'm trying to find out, What am I trying to do about sexual preference? Am
I trying to change peoples' sexual preference? I think the argument that
it's interesting to know whether genes influence or don't influence, for
example, sexual preference is a bad argument. I don't want to know that, I
don't care, it doesn't mean anything to me.

[Sound of Doug and Dave in the kitchen, rattling dishes, talking.]

JACKIE NORTHAM: But back in the Widener kitchen, the debate about genetics and sexual preference strikes an emotional chord with the twins. Dave, the older twin by four minutes, has fears about the repercussions of genetic research.

DAVE WIDENER: Just think about it, if there is a gene that says, say that you know gray eyes are unattractive, you know, if we could filter out a gray eye gene, you know, that would be scary and parents can say let's filter out this gene. And parents can say, let’s filter out this gene, you know.

JACKIE NORTHAM: But his brother Doug says research can only go so far in determining a person's behavior.

DOUG WIDENER: No matter how similar Dave and I are, I'm…I’m unique and
there'll never be another Doug Widener on this planet ever, you know, that exhibits exactly the exact same traits that I do.

JACKIE NORTHAM: Which is why it will likely be a long time, if ever, before scientists can understand the complex interaction of nature and nurture.

[Theme Music]

JOHN HOCKENBERRY: Jackie Northam found that the influence of heredity in homosexuality is a complex and touchy issue. People's opinions about the scientific work done in this area are often colored by their feelings about homosexuality itself. Pilar Ossorio:

PILAR OSSORIO: Certainly there's a portion of society today, which is very opposed to homosexuality, which considers it a lifestyle, a choice and more than that, considers it a sin. So, you could ask, "Will doing this research change people's attitudes in any way?" And particularly, will this diminish the stigma that's associated with homosexuality in any way? Will it cause people to change their attitudes and become more accepting or understanding of homosexuality?

JONOTHAN MARKS: Whether or not homosexuality is genetic is not going to influence what homophobes or homophiles think about the behavior. Their attitude is going to be framed independently of what science has to say.

JOHN HOCKENBERRY: Jonathan Marks is a biological anthropologist at the University of California at Berkeley.

JONOTHAN MARKS: The Nazis felt that homosexuality was inherited, and that therefore to get rid of homosexuality, all you had to do was kill all the homosexuals. The reaction to that after the war, of course, was to say, "Well, it's not genetic. It's learned." And this was conventionally
accepted wisdom until homophobes discovered that homosexuals were teaching in the public schools and said, "Well, if homosexuality is a learned behavior, we can't have homosexuals teaching our children, can we? Because they'll be teaching our children buggery." This does have social consequences.

JOHN HOCKENBERRY: The question is, do people mostly choose their personality traits from some preference, or do they live out some predetermined organic scenario in their personalities? The debate is the high voltage that drives so many controversial issues in policy and politics. Let’s take the question of addiction. If addiction is a choice, you would deal with it one way. But if it’s beyond our control and we can prove that addiction is genetically determined, it would suggest a completely different strategy.

[Sound of jukebox at the bar; loud voices in background]

BARTENDER #1: We get a little of everything, I mean you have....we have a lady who comes in here and basically, drinks half a bottle of wine, takes off, comes back a couple of hours later, and orders the other half bottle of wine. You will have your regulars. They just need their, their fix I
guess.

JOHN HOCKENBERRY: What makes someone an alcoholic? What exactly do we mean by an "addictive personality"? Lee Silver studies this trait:

LEE SILVER: When a person becomes addicted to a substance they have a craving for that substance. And they also have withdrawal symptoms. So, if the stop smoking or they stop taking alcohol they get sick from not having the drug and they need the drug to overcome their sickness.

JOHN HOCKENBERRY: What distinguishes someone who is addicted to alcohol from the rest of us who might simply have one too many at a party?

LEE SILVER: Addiction has to be distinguished from abuse. It's not just a question of how much alcohol is drunk; it's a question of whether the alcohol is being drunk because of a need, a physiological need, to do the drinking. So there are actually many college students who over drink,
abuse alcohol in a serious way every weekend during their college career; they graduate college, they grow up and they never have a problem with alcohol because they never became addicted.

JOHN HOCKENBERRY: But why can some people control their drinking and others can't?

LEE SILVER: Some people are born with a genetic predisposition towards addiction. So that these people have a particular genetic constitution that when they drink, they will become addicted.

JOHN HOCKENBERRY: So do certain genes make one an addict? Not really. They are simply codes from which proteins are manufactured. These proteins play an important role in mind and body function.

LEE SILVER: Genes operate very indirectly. They are the instructions for making proteins. And these proteins carry out different functions in our body. So, some proteins operate to digest the food that we eat every day. And other proteins act as receptors to receive neurotransmitter signals.

JOHN HOCKENBERRY: Neurotransmitters, in turn, allow signals in our brain to be sent from one nerve cell to the next -- the basis of brain function. Two neurotransmitters -- serotonin and dopamine -- seem to play a crucial role in the sending and receiving of signals which influence our
personality.

LEE SILVER: Serotonin and dopamine are used by nerve cells that play a roll in personality traits and in emotive kinds of behaviors – things like curiosity, anxiety, aggression.

JOHN HOCKENBERRY: How did scientists figure out this gene-protein-neurotransmitter connection? Well, it's now possible to actually isolate the DNA from an animal's cells in order to, in theory, identify specific genes that might influence personality traits. So, while twin studies
may still provide useful information, geneticists can now design studies that look at the genes themselves. Animal studies offer an important model for scientists who hope their results will eventually apply to humans. Studies of mouse DNA look especially promising. One behavior being intensively examined is addiction. In these studies, scientists have isolated specific genes that seem to help regulate the use of both serotonin and dopamine in the brains of mice.

Robin Marks reports now on a research team looking at neurotransmitters at the Veterans Administration Medical Center in Portland, Oregon:

ROBIN MARKS: Science has a long, if some what checkered, history of animal experimentation. Remember Pavlov's dog? That research formed the backbone of our knowledge on behavioral conditioning. Dogs, cats, monkeys and mice continue to be used in behavioral studies and today that includes the genetics of behavior. Researchers are particularly interested in behaviors associated with disease, such as alcoholism.

[Sound of laboratory; people talking]

ROBIN MARKS: The Veterans Administration Medical Center has a wing filled with mice, cages and testing apparatus. Some of the testing devices are simple constructions-- no more complicated than the police test of walking a straight line. Others are a bit more elaborate. Behavioral geneticist Tamara Phillips:

[Sound of cage opening]

TAMARA PHILLIPS: This is called a grid test and it measures end coordination produced by drugs. So, normally an animal, when you place it in this chamber, there is a grid floor, it will walk around on that grid floor -- it’s just made of hardware cloth -- without it's feet slipping through. But if you give it alcohol it becomes very ataxic and discoordinated and it's feet start to slip through and make contact with this metal plate, that's lying here.

ROBIN MARKS: Given an adequate amount of alcohol, all mice will stumble on the grid. But, says Phillips, the mice who stumble less may have a greater chance of becoming addicted. This test helps researchers isolate how sensitivity to alcohol fits into the addiction process. The research group conducts a variety of experiments that look at discrete parts of the process. Some experiments look at differences in preference for alcohol. Others examine how much mice come to tolerate alcohol's effects. And still others test a rodent's reaction when alcohol is taken away.

JOHN CRABBE: You pick them up by the tail and there's a very mild -- like a tremor and convulsion that they have that human alcoholics would have too if you didn't give them valium in the ER.

ROBIN MARKS: John Crabbe is Director of the Portland Alcohol Research Center and a behavioral neuroscientist.

JOHN CRABBE: …get better over twenty four hours. So we monitor that sign to estimate how dependent they were and there's big individual differences. Some of them show nothing at all, some of ‘em show big long signs of dependence.

ROBIN MARKS: To search for genes associated with dependence, Crabbe and Phillips breed mice with severe withdrawal signs together and mice with mild withdrawal signs together. By creating mice whose behavior is at either extreme, researchers can test for genetic differences. John Crabbe
says this research method will eventually help locate similar genes in people.

JOHN CRABBE: Cumulatively over a lot of different kinds of experiments and approaches you can use it to identify the specific genes that have been changed by that breeding program and 85% of our genes are the same as what mice have. So, that if you can find genes that lead to extreme responses in mice, it's very likely then that you would then know where to look in humans for the same genes.

ROBIN MARKS: Mouse studies have disadvantages. Mice can’t tell scientists about peer pressure or other social influences. Also, mice are very inbred, humans are not. And that makes the genetic correlation between mice and people harder to do. But Tamara Phillips says there is one huge advantage.
TAMARA PHILLIPS: For me it’s being able to control the environment so that I can separate that out from the genetics and actually determine what part of this behavior is genetically determined, what part of this behavior is environmentally determined. It's extremely difficult to do that in human populations.

ROBIN MARKS: Controlling the genetic makeup of mice is another key advantage. Phillips and Crabbe occasionally use " knockout mice"—mice with a specific gene removed or knocked out. Phillips and Crabbe use knockout mice for studies involving dopamine and serotonin – brain chemicals that affect mood and motivation in people -- including, perhaps, the ability to control the impulse to drink. John Crabbe:

JOHN CRABBE: These animals grow up lacking one of the fourteen different kinds of serotonin receptors and it turns out they drink twice as much alcohol by choice as their normal counterparts. So that is pretty suggestive that that gene is playing a fairly important role.

EVAN BALABAN: If I tell you there's a gene that seems to be correlated, that variation in this gene is correlated with variation in a behavior, what have I explained by telling you that? (chuckle) I really haven't explained very much. 3330

ROBIN MARKS: Evan Balaban is a senior research fellow at the Neurosciences Institute in San Diego. He says alcoholism isn't just a biological problem and genetics is a narrow lense through which to view addiction.

EVAN BALABAN: Whatever John Crabbe is studying will have some bearing on understanding how alcohol is metabolized in a body and the effects that alcohol has on cells of the body, including cells of the brain. And the problem with going from that to statements about alcoholism is that alcoholism is much more complicated than that, because it involves things about emotions and thoughts and feelings that are in and of themselves not directly connected to the way that cells are metabolized or affected by alcohol.

ROBIN MARKS: Balaban's arguments are bolstered by the fact that results from mouse studies don't always hold up in human studies. It's difficult to know why. Environment, study design, differences not yet understood between mice and people, could all be factors. Crabbe says it's important to chisel away at these questions and over time the larger picture will
emerge.

JOHN CRABBE: There isn't a gene for alcoholism. There's not five genes for alcohol. Any of us doing this work would weigh in an say, OK, maybe there's 10, maybe there's 50. It's hard to tell the
difference once you get above about three. These aren’t major gene disorders. They’re polygenic disorders, so there are lots of genes out there and we assume that each one of them notches up or down your risk by a little bit. So what you have to do is capture enough of them that in the aggregate you can really get a handle on increasing or decreasing risk.

ROBIN MARKS: DNA can only tell part of the story of human addiction. Just how large or small a part genes play is far from known. For now these researchers proceed on the hope that deeper knowledge of alcohol addiction will one day lead to better treatment of a difficult disease.

[Theme Music]

JOHN HOCKENBERRY: This is The DNA Files.

JOHN HOCKENBERRY: This is The DNA Files. I’m John Hockenberry. You often hear people say, "if he really wanted to stop drinking, he would." But it may not be so simple. Robin Marks found that genetics may play an important role in addiction. And as we understand more about addiction, how will that research change our attitudes outside of the laboratory? Lee Silver and Pilar Ossorio:

LEE SILVER: I think when an alcoholic person who has such a hard time stopping drinking discovers that he is addicted because of something in his genes, it could give him a sense of relief. It's taking away the notion that the reason people are alcoholic is because they have a character flaw.

PILAR OSSORIO: We tend to think that if we can discover a biological basis for some behavior that that somehow diminishes the responsibility that a person has for doing that behavior. Well, everybody might have propensities to do something that our society disapproves of. And it's one's obligation to overcome that propensity.

JOHN HOCKENBERRY: Can genetic research ultimately help overcome a propensity towards alcoholism?

LEE SILVER: If we understand the molecular basis for addictability, we may be able to find a cure for it. If we understand the genes, we'll be able to figure out what proteins those genes make and then hopefully we'll be able to figure out a way of overcoming the addiction much more easily.

JOHN HOCKENBERRY: And some people worry that finding a genetic propensity may lead to dangerous consequences. Tests for drug abuse are now common. Why not tests for a genetic propensity towards drug abuse or alcoholism?

PILAR OSSORIO: There's also a concern that there might be problems with discrimination--job discrimination, discrimination of people's ability to get into the military, discrimination in terms of their ability to get insurance. This is a really pretty serious concern.

LEE SILVER: Just because somebody is addictable to alcohol does not mean that they're going to be drinking on their job. And so their genetic profile should not be used. The way they behave should be used.

JOHN HOCKENBERRY: Alcoholism and homosexuality are both emotionally charged issues. Geneticists are also curious about some less controversial traits -- ones that we all share to some degree or another. They call them "normal-range" personality traits. Whether you tend to be happy-go-lucky or have a grumpy disposition, whether you are a quick study in school or struggle with every test, whether you have perfect pitch, a quick sense of humor or a hot temper -- these are all controlled -- at least in part – by the genetic make-up of your DNA. Dr. Robert McCrae:

ROBERT MCCRAE: Talkativeness is a normal range trait, because there's all kinds of variation and some people are very talkative, some people are not talkative at all, and most of them are somewhere in between. And you don't have to have a disorder of some kind to be relatively silent or to be relatively talkative.

JOHN HOCKENBERRY: One group of traits that psychologists like Robert McCrae are looking at are called "novelty-seeking".

ROBERT MCCRAE: People who are high in novelty seeking are extroverted and they are cheerful, and active and fond of excitement. So they're not persistent, they are not deliberate and cautious.

JOHN HOCKENBERRY: But what makes one person love going to parties filled with strangers and someone else prefer to stay at home with a great book? Geneticists are studying a number of what scientists call "normal-range" traits to try to figure out how much is genetically based
and how much is environmentally influenced. Which genes actually play a role and how they do it?

[Sound of New York City Street; people and cars]

JOHN HOCKENBERRY: The first step for these researchers is to determine the level of a trait -- like novelty seeking for instance -- that an individual test subject may have. How do they do this? They simply ask people. The researchers give them "personality quizzes" like this one I'm holding right now, as I wander down Manhattan's 5th avenue. There must be plenty of thrill-seekers in this crowd.....You, you -- excuse me. Can I ask you a couple of questions? I work for Public Broadcasting. My name is John Hockenberry. How are you?

EMILY: I’m fine.

JOHN HOCKENBERRY: We're doing a program on personality and genetics. OK. And I just want to give you a very short personality quiz to see if we can learn anything about you. Alright?

EMILY: Uh oh.

JOHN HOCKENBERRY: Your response to these questions should be “agree,” “strongly agree,” “disagree” or “strongly disagree.” Alright? OK.

EMILY: OK.

JOHN HOCKENBERRY: And what's your name?

EMILY: Emily.

JOHN HOCKENBERRY: Emily. Alright. Emily. Do you think it’s conceivable that your personality is genetically based?

EMILY: Yes.

JOHN HOCKENBERRY: Really?

EMILY: Yeah.

JOHN HOCKENBERRY: Now, if they determine to some precise degree how genetically based your personality was, would you take it in for an overhaul?

EMILY: What do you mean? Like can you rephrase that?

JOHN HOCKENBERRY: Yeah, if they could…if you could manipulate your personality by…

EMILY: Oh, by genetically changing it?

JOHN HOCKENBERRY: Yeah. Right.

EMILY: No.

JOHN HOCKENBERRY: You wouldn’t change anything?

EMILY: No.

JOHN HOCKENBERRY: Would you suggest that she change something?

[group laughs]

MALE COMPANION: No. No. I wouldn’t suggest it at all.

JOHN HOCKENBERRY: Good. Alright.

EMILY: Not even my sense of direction?

[group laughs]

MALE COMPANION: OK. That’s right - sense of direction.

JOHN HOCKENBERRY: So, if you could get a better sense of direction genetically, you’d do that?

MALE COMPANION: Yeah

EMILY: Yeah, probably.

MALE COMPANION: If possible.

[music]

JOHN HOCKENBERRY: Um…what’s your name?

DIANE: Diane.

RICK: Rick.

JOHN HOCKENBERRY: OK. How would you respond to this question. And your answers can be “agree,” “strongly agree,” “disagree” or “strongly disagree.” OK? “I like to try new foods that I've never tasted before.”

DIANE: Strongly agree.
JOHN HOCKENBERRY: Strongly agree. And you?

RICK: Strongly disagree.

JOHN HOCKENBERRY: Strongly disagree...whoa. whoa!

DIANE: He's very rigid when it comes to food. He does not like to try new things and so...

JOHN HOCKENBERRY: I see....

RICK: But I'll get on a plane and go to Thailand for a month so...

DIANE: Right.

JOHN HOCKENBERRY: With a lot of hamburgers I guess....

DIANE: Right. He won’t…he won’t eat the food there.

[music]

JOHN HOCKENBERRY: …a personality quiz, is that OK?

BRYCE: Sure.

JOHN HOCKENBERRY: Alright, what's your name?

BRYCE: Bryce.

JOHN HOCKENBERRY: And your name?

NIKA: Nika

JOHN HOCKENBERRY: Great. This is an actual personality test that, you know, psychiatrists and psychologists have developed.

BRYCE: Uh oh.

JOHN HOCKENBERRY: 'I have no patience with dull and boring persons.'

BRYCE: Disagree.
JOHN HOCKENBERRY: Disagree.

NIKA: Strongly disagree.

JOHN HOCKENBERRY: Strongly disagree? So you have......

NIKA: Nobody's dull to me.

JOHN HOCKENBERRY: Oh really?

NIKA: No.

JOHN HOCKENBERRY: So you have infinite patience for dull and boring people. That's…that’s a personality trait.

BRYCE: We're putting up with you aren't we?

[laughter]

JOHN HOCKENBERRY: There you go!

BRYCE: Just kidding.

JOHN HOCKENBERRY: I opened the door, and you broke through.

[music]

JOHN HOCKENBERRY: So, I’ve made some new friends here but what have I learned. Psychologists like Robert McCrae spend years designing just the right balance of questions in these sorts of tests.

ROBERT MCCRAE: The most common way to assess personality is by asking people to describe themselves in terms of a fixed set of questions that are relevant to whatever it is you’re trying to measure. Any one single answer may not be very accurate, and you want to make sure you that understand what the person is trying to say by asking a similar question many times

JOHN HOCKENBERRY: But just how useful is a test like this? Jonothan Marks thinks these tests have little value.

JONOTHAN MARKS: The problem with self identifications, especially for things like personality or behaviors is that people either kid themselves or they kid you about what they really are. There is no doubt in my mind that in most cases, and for most purposes you can evaluate people’s personalities reasonably well. And the evidence from that comes from many many studies showing that these assessments predict responses to a particular situation.

JOHN HOCKENBERRY: A bigger question is whether the whole idea of normal range traits is valid. Is there even such a thing as novelty seeking? Marks proposes that these traits are not inherent in the human species but varied between cultures.

JONOTHAN MARKS: Americans today, for example, are very very homogeneous in their behaviors. Sure, Newt Gingrich and Jessie Jackson might look different, sound different, act different. But on a global scale, if you take the most heterogeneous group of Americans and put them in a room, the one sherpa from Nepal is going to stand out very very distinctively. And the difference between that one sherpa from Nepal and all of those heterogeneous Americans is not genetic. It’s cultural. It’s the result of historical, social processes that have nothing whatsoever to do with genetics. Behavioral differences in the human species occur much more extensively between groups of people than they do within groups of people.

ROBERT MCCRAE: We have to make a distinction here I think between traits and behaviors. Personality traits are dispositions. They’re tendencies. Behaviors can be different in different cultures. They can be different at different points in the life span. Shooting guns is not something that you have a gene for. But being aggressive may well be something that is influenced by genes.

JOHN HOCKENBERRY: Robert McCrae says that if you are an aggressive person, it doesn’t matter where in the world you live. You are going to find ways to be aggressive.

ROBERT MCCRAE: You may use guns. You may use knives. You may use harpoons. But human beings have found ways to be aggressive in every possible circumstance. And if you have that personality trait, you’ll find a way to express it. So, we have to distinguish between the underlying tendency that’s very general and abstract, a very broad potential and then the concrete behaviors that express it, that act it out at any particular time and place.

JOHN HOCKENBERRY: Traits like nurturing and aggression are also being studied through animal models, the human and mouse genome are very similar, so that often the same gene produces the same protein which influences the same neurotransmitter. But whether this neurotransmitter actually results in the same personality trait, is still very much in question. Mouse studies can’t tell us everything. Scientists are now conducting studies with humans as well as animals to identify specific genes which influence personality traits. These are called genetic association studies. Dean Hamer is best known for these studies. His earliest genetic association studies were about gay men. These were highly criticized some say because the science was faulty. Others say because the subject matter was too controversial. In any case, Hamer has refined his research and he is now studying thrill seeking. While there is no single gene that’s responsible for making a person a thrill seeker, some genetic association studies have identified a candidate gene which seems to play a role. Reporter Kathy Merritt will tell us all about it.

KATHY MERRITT: It seems a little ironic that the search for a thrill seeking gene is happening in a place not exactly known for big thrills, a laboratory. This lab is at the National Institutes of Health in Bethesda, Maryland. And here, under the fluorescent lights amidst the test tubes and computers and stacks of boxes, molecular biologist Dean Hamer has been doing the painstaking work of trying to link behavior and genes.

DH: There obviously are a lot of different factors that guide a person’s behavior, the way you were brought up, where you went to school, who you’ve met, what happened to you yesterday, what happened to you twenty years ago. But we also think that a person’s genes are very important.

KATHY MERRITT: Hamer and a colleague in Israel, Richard Epstein, both began doing studies that tried to link thrill seeking, they call it novelty seeking, with a particular gene. Epstein is director of research at Hertzog Hospital in Jerusalem. He says the study actually began outside the lab with a questionnaire.

RICHARD EPSTEIN: It’s a hundred questions and they answer yes or no to questions like, I enjoy getting up in the morning and doing the same thing at work that I did yesterday. And if you answer yes to that question, you get a low score for novelty seeking.

KATHY MERRITT: Once the answers were tallied, people were rated as high novelty seekers or low novelty seekers. The scientists then gathered DNA samples from their subjects either by scraping a few skin cells off their cheeks or making them swish a saline mouthwash or drawing blood. Then they burst open the cells with a strong detergent, added a chemical to extract the DNA, and purified the DNA using a centrifuge.

[Sound of centrifuge and timer rings]

KATHY MERRITT: But how did they know which gene to look at?

RICHARD EPSTEIN: The particular gene we chose is in a class of genes that are brain receptors for a chemical called dopamine.

KATHY MERRITT: Dopamine is a neurotransmitter. It helps brain cells communicate with each other. And Epstein says previous studies show that it might be involved with impulsive behavior. So, it made sense to study the gene called D4DR. It makes a protein that helps process dopamine. Dean Hamer says they started comparing the gene from one person in the study to the next.

DEAN HAMER: We found there was a difference in that gene. Some people have what’s called a long form of the gene. Other people have a short version of the gene.

KATHY MERRITT: And when they compared the questionnaire results with the genetic differences, the scientists believed they found that people with the long form of the gene had scored higher on novelty seeking than people with the short form. Was this it, then, a gene for novelty seeking?

DEAN HAMER: Of course the gene doesn’t whisper into your ear, “Go bungee jumping.” Genes aren’t that smart or that powerful. The gene just makes a receptor for dopamine. The key point is that people with one form of the gene make a receptor that’s a little bit more sensitive to dopamine. People with the other form of the gene make a receptor that’s a little bit less sensitive to dopamine. Presumably what happens is that when those two people do a new activity like bungee jumping, they release the same amount of dopamine in the brain. But depending on which form of the receptor they have, that either feels good or it feels bad.

KATHY MERRITT: Hamer and Epstein thought they found a connection. But despite their conclusion, there’s a problem with their research. Other scientists have had mixed results in trying to replicate the findings.

AM: In our hands there was no relationship between the dopamine D4 receptor gene and the individuals with high novelty seeking.

KATHY MERRITT: Anil Malhotra is chief of the molecular psychiatry unit at Hillside Hospital in Long Island, New York.

ANIL MALHOTRA: And in fact, in one population of subjects found the opposite association, that the patients were the subjects with the low levels of novelty seeking were linked to this particular form of the gene.

KATHY MERRITT: Malhotra says there are lots of reasons why scientific studies don’t replicate. For one thing, his study used subjects from a different population group. They were all from Finland.

ANIL MALHOTRA: They’re a very special population genetically, meaning that they haven’t interbred for generations and generations with outsiders. The other studies -- one study was a U.S. study, which is a fairly intermixed population. The other study was an Israeli group. So, those are different populations of people, and perhaps these relationships exist in Israel and in the U.S. population studies and not in Fins.

RUTH HUBBARD: There is a basic flaw in all of this research.

KATHY MERRITT: Ruth Hubbard is a retired professor of biology at Harvard and a board member of the Council For Responsible Genetics. She says the human genome is so big and people are so different that you can’t just study one small group of people and say the results apply to everybody.

RUTH HUBBARD: You could, in fact, by focusing on the right thing and structuring the way you wanted to structure it, you could get any result you wanted. You could always come up with a genetic linkage to the trait that you are trying to prove is genetic and inborn, and biological. And then a little more research, or a good deal more research, is going to throw it out.

KATHY MERRITT: Even the scientists doing the research say that genes don’t determine behavior. In fact, Hamer and Epstein say the D4DR gene has only about a five or six percent influence over novelty seeking behavior. As many as ten other genes may play a role. But Epstein says genes can help move people in a particular direction.

RICHARD EPSTEIN: You could have a bank robber who is very flamboyant and very dramatic, and you could have a bank robber who’s uh…very quiet and…and goes about his work in a very undramatic fashion. And similarly you could have a research scientist who can be very dramatic and broadcasts his enthusiasm to everyone, and a research scientist who does things very quietly. The critical issue for society is why one person decides to be a bank robber and another person decides to be a research scientist. The “how’ we decide to do it -- the manner and the style -- is due to genes. But the “what” and the “point” of our behavior and the goals that we set for ourselves are much more influenced by parents, and society, and the culture that we live in.

[Theme music]

KATHY MERRITT: Epstein and Hamer say the next decade will see an explosion of research in behavioral genetics. Their studies are the first of many that will try to tell us just how much of our personality comes from our DNA.

JOHN HOCKENBERRY: Kathy Merritt learned that it may be a long time before we have conclusive results in genetic research. Even so, the work of geneticists like Dean Hamer is often sensationalized in the press. [rustling paper] Let me give you some examples here. Let’s see. Grumpy, fearful, neurotics appear to be short on a gene. That’s the New York Times, November 29, 1996. Here’s another one. Scientists hope cheap date gene defect can be found in humans too. I’d be interested in that. L.A. Times, June 12, 1998. Or how about this? Study provides new evidence of “gay gene”, Washington Post, October 31, 1995.

PILAR OSSORIO: If we call something a “gay gene”, then that can really mislead people into thinking, oh, gay people are so different because they have some gay gene that I don’t have.

JOHN HOCKENBERRY: Dr. Pilar Ossorio.

PILAR OSSORIO: They don’t realize, well, we basically all have the same genes. And so that kind of reporting and that kind of labeling, it is misleading.

JOHN HOCKENBERRY: Jonathon Marks claims that the real culprit isn’t the media but the scientists themselves.

JONOTHAN MARKS: The training of the average geneticist is to learn how to run gels, to learn how to work the equipment that has the flashing multi colored lights, but not to learn the humanistic aspects, the bioethics, the history that defines the work as meaningful, that defines the work as socially relevant. And that scientist who has had technical training no longer has the luxury of denying the social relevance, of denying their own responsibility for the work that they do.

PILAR OSSORIO: There’s no such thing as pure research. And I think it’s especially important for scientists who are doing things like behavioral genetics which is very controversial, which touches on issues such as sexuality, such as violence, such as alcoholism. It touches on issues which are contentious and contested in this society. And so, I think it’s particularly important in those cases for scientists, in order to be able to do good science, to be very very self examining about what our thought patterns, and structures, and preconceptions are. Because if science which is not very good is incorporated into social policy, a lot of people’s lives can be hurt.

JOHN HOCKENBERRY: Jonathon Marks says that happened in the 1920s when there was a great deal of publicity about the influence of genetics.

JONOTHAN MARKS: What geneticists were emphasizing is how important genetics was in American life. What we needed to do was to improve the gene pool of the American people and the most immediate result of that particular social movement led by the scientists was discrimination, was the violation of civil rights, was the restriction of immigration, was the involuntary sterilization of the poor on a very large scale. The tragedy is that this era of genetics is generally not part of the training of the average geneticist and it needs to be.

JOHN HOCKENBERRY: Jonothan Marks is referring to the eugenics movement of the early 1900s. At that time unfounded assumptions about the heritability of character traits led to oppressive social policies in a number of countries. Particularly here in America. Women who were branded as feeble minded, criminal or insane were forcibly sterilized to prevent them from passing these traits on. The argument was that it was inefficient to allow such “problem parents” to produce offspring which the government would then have to support. By 1935, 30 states and Canadian provinces had sterilization laws on the books. Ultimately over 60,000 women were sterilized under these eugenics laws.

[Theme music]

JOHN HOCKENBERRY: That’s our painful past. But what about the future? As our understanding of genetics and personality grows, will we remember the lessons of the past? Do we understand the social impact of our scientific discoveries? And what will we do with that knowledge? Who decides how and whether a person’s personality needs improvement? And who decides what is socially unacceptable behavior? If you are hyperactive, are you also more curious? If you’re a thrill seeker, are you also more liable to break the law? Do we want to cure shyness or disruptive behavior? A seemingly endless quest for knowledge surely must be a genetic trait of the human species. But often our ability to discover how things work races ahead of our ability to consider the implications of our actions. How do we handle the knowledge we’re uncovering? This is a question not only for the scientists but also for the rest of us.

[Theme music]

Credits for The DNA Files:

The DNA Files is produced by SoundVision Productions and is made possible through the generous contributions of the National Science Foundation, the Department of Energy and the Alfred P. Sloan Foundation.

For more information, and for an interactive look at some of the issues behind this program, go to our web site at www.dnafiles.org. For tapes and transcripts of this program and this series, contact VisABILITY at 303.823.8000. To contact The DNA Files, send your email to feedback@dnafiles.org. This program, "DNA and Behavior: Is Our Fate in Our Genes?", was produced by Claire Schoen with reports from Jackie Northam, from WBEZ; Kathy Merritt, from WAMU; Loretta Williams and Robin Marks. The engineer was Robin Wise and the editor was Sora Newman. The DNA Files Executive Producer is Bari Scott. The Project Director is Jude Thilman.

Managing Editors of The DNA Files are Loretta Williams and Catherine Stifter. Production manager is Catherine Gollery. Technical Director is Robin Wise. Adi Gevins is Director of Research and Creative Consultant. Sally Lehrman is Content Consultant. Original music composed and performed by Bill Frisell. Introductory Feature produced by John Rieger and edited by Gary Covino.